Zhang Congdang, Wang Yi, Ma Shuzhi, Li Leike, Chen Liyun, Yan Huimin, Peng Tao
1 School of Life Sciences, Anhui University , Hefei, China .
2 Southern China United Vaccine Institute , Guangzhou, China .
Viral Immunol. 2016 Jun;29(5):288-95. doi: 10.1089/vim.2015.0110.
Human enterovirus 71 (EV-A71), a major agent of hand, foot, and mouth disease, has become an important public health issue in recent years. No effective antiviral or vaccines against EV-A71 infection are currently available. EV-A71 infection intrudes bodies through the gastric mucosal surface and it is necessary to enhance mucosal immune response to protect children from these pathogens. Recently, the majority of EV-A71 vaccine candidates have been developed for parenteral immunization. However, parenteral vaccine candidates often induce poor mucosal responses. On the other hand, oral vaccines could induce effective mucosal and systemic immunity, and could be easily and safely administered. Thus, proper oral vaccines have attached more interest compared with parenteral vaccine. In this study, the major immunogenic capsid protein of EV-A71 was displayed on the surface of Saccharomyces cerevisiae. Oral immunization of mice with surface-displayed VP1 S. cerevisiae induced systemic humoral and mucosal immune responses, including virus-neutralizing titers, VP1-specific antibody, and the induction of Th1 immune responses in the spleen. Furthermore, oral immunization of mother mice with surface-displayed VP1 S. cerevisiae conferred protection to neonatal mice against the lethal EV-A71 infection. Furthermore, we observed that multiple boost immunization as well as higher immunization dosage could induce higher EV-A71-specific immune response. Our results demonstrated that surface-displayed VP1 S. cerevisiae could be used as potential oral vaccine against EV-A71 infection.
人肠道病毒71型（EV - A71）是手足口病的主要病原体，近年来已成为一个重要的公共卫生问题。目前尚无针对EV - A71感染的有效抗病毒药物或疫苗。EV - A71感染通过胃黏膜表面侵入人体，因此增强黏膜免疫反应对于保护儿童免受这些病原体侵害至关重要。最近，大多数EV - A71候选疫苗是为肠胃外免疫而研发的。然而，肠胃外候选疫苗通常诱导较差的黏膜反应。另一方面，口服疫苗可诱导有效的黏膜和全身免疫，且易于安全给药。因此，与肠胃外疫苗相比，合适的口服疫苗更受关注。在本研究中，EV - A71的主要免疫原性衣壳蛋白展示在酿酒酵母表面。用表面展示VP1的酿酒酵母对小鼠进行口服免疫可诱导全身体液和黏膜免疫反应，包括病毒中和滴度、VP1特异性抗体以及脾脏中Th1免疫反应的诱导。此外，用表面展示VP1的酿酒酵母对母鼠进行口服免疫可使新生小鼠免受致死性EV - A71感染。此外，我们观察到多次加强免疫以及更高的免疫剂量可诱导更高的EV - A71特异性免疫反应。我们的结果表明，表面展示VP1的酿酒酵母可作为潜在的口服疫苗用于预防EV - A71感染。
